Beyond the root: licorice (Glycyrrhiza glabra L.) fruit extract modulates oxidative stress and apoptotic markers in...

The rising global prevalence of neurodegenerative disorders underscores the urgent need for novel therapeutic strategies. Oxidative stress is a well-established central driver in the pathogenesis of conditions like Alzheimer's and Parkinson's disease. While the root of Glycyrrhiza glabra L. (licorice) is a renowned source of natural antioxidants, its fruit remains a largely unexplored reservoir of bioactive compounds with potential neuroprotective properties. This in vitro study aimed to systematically evaluate the neuroprotective potential of different licorice fruit extracts and elucidate the underlying mechanisms against hydrogen peroxide (H₂O₂)-induced oxidative damage in PC12 neuronal cells. Different licorice fruit extracts were prepared sequentially with n-hexane, chloroform, ethyl acetate, methanol, and water by the maceration method. The protective effects of these extracts against H₂O₂-induced cytotoxicity were assessed using the MTT assay. Phytochemical profiling of the active ethyl acetate extract (EA extract) was performed using TLC, total flavonoid assay, and HPLC-DAD. EA extract exhibited the strongest protective activity. Pre-treatment with non-toxic concentrations of EA extract (12.5 and 25 µg/mL) significantly increased cell viability against H₂O₂ (IC₅₀ = 70 µg/mL approximately 2.06 mM) by 33% and 38%, respectively. This extract possessed the highest total flavonoid content (50.08 ± 0.31 mg of quercetin equivalents per gram of dry extract) among all extracts, and HPLC-DAD analysis confirmed the presence of glabridin 27.75 ± 0.01 mg per gram of dry EA extract. EA extract also notably restored mitochondrial membrane potential, reduced caspase-3 activity, and decreased ROS production in H₂O₂-stressed cells. Our findings indicate that the ethyl acetate extract of licorice fruit attenuates H₂O₂-induced oxidative stress in PC12 cells, and its neuroprotective effect is likely associated with its high flavonoid content. Further research on licorice fruit may facilitate the discovery of novel therapeutic agents for oxidative stress-related disorders.